Reference to any prior art in the specification is not, and should not be taken as, an acknowledgment or any form of suggestion that this prior art forms part of the common general knowledge in Australia or any other jurisdiction or that this prior art could reasonably be expected to be ascertained, understood and regarded as relevant by a person skilled in the art.
The incidence of cancer in companion animals, such as dogs and cats and the like is increasing, and cancer is now considered to be the leading cause of death in older animals. It is believed that the annual incidence rate for cancers in dogs is about 2 to 2.5% (about the same as humans) and about 1.5 to 2% for cats.
The cancers having the highest incidence in dogs are in the following order: lymphoma (about 20%); mast cell tumor (about 18%); soft tissue sarcoma (about 10%); hemangiosarcoma (about 10%); osteosarcoma (about 9%). The remaining segments typically include squamous cell carcinoma, mammary carcinoma, melanoma, histiocytoma and fibrosarcoma.
The cancers having the highest incidence in cats are in the following order: lymphoma (about 25%); mast cell tumor (about 22%—of cutaneous neoplasms); squamous cell carcinoma (>11% of cutaneous neoplasms); mammary carcinoma (about 10%); and the remaining segments include hemangiosarcoma, osteosarcoma, fibrosarcoma, sebaceous hyperplasia/adenoma.
Approaches to cancer treatment in veterinary oncology include surgery, radiation therapy, hyperthermia therapy, photodynamic therapy and chemotherapy. Gene therapy and immunotherapy have not been widely implemented.
Apart from Palladia (toceranib phosphate; Pfizer), no medicines have been given marketing approval for use as chemotherapeutics for cancer treatment in companion animals. This is mainly because of the high costs associated with obtaining marketing approval.
In most jurisdictions, veterinary oncologists have “off-label” drug use privileges. Off-label drug use means that the veterinary oncologist can use drugs approved for one species (including humans) freely in another species. With these privileges, a common practice has arisen in veterinary oncology whereby the oncologist tends to select those chemotherapeutics for use in cancer treatment of companion animals for which significant clinical experience has been obtained in human oncology.
Examples of chemotherapeutics and relevant indications currently used in veterinary oncology are shown in Table 1.
TABLE 1ChemotherapeuticType of cancerAlkylating agentsCyclophosphamide (Cytoxan)Lymphoma, mast cell tumors,mammary tumors, hemangiosarcomasIfosfamide (Ifex)Chemoresistant lymphoma, soft tissuesarcomaChlorambucil (Leukeran)Leukemias, mast cell tumors,lymphomaMelphalan (Alkeran)Multiple myelomaBusulfan (Myeleran)LeukemiasProcarbazine Hyd (Matulane)LymphomaPlant alkaloidsVincristine (Oncovin)Lymphoma, venereal tumors,mast cell tumors, sarcomasVinblastineLymphoma, mast cell tumorsAntimetabolitesMethotrexateLymphoma, osteosarcomaCytosine arabinosideCNS lymphoma, leukemia(Cytostar, Ara-C)FluorophyrimidinesSkin tumors, mammary carcinoma,(Fluorouracil [5-FU])GI tumorsHydroxyureaRecurrent leukemiasAntitumor antibioticsDoxorubicinLymphoma, hemolymphatic(hydroxydaunomycin)malignancies, carcinomas andsaracomas including osteosarcomaEpirubicin (Pharmorubicin)LymphomaMethoxymorpholinodoxorubiconChemoresistant lymphoma, sarcomasand carcinomasMitoxanthroneOral squamous cell carcinoma,lymphoma, sarcomas and carcinomasBleomycinSquamous cell carcinomaActinomycin DLymphoma, sarcoma, carcinomaPlatinum compoundsCisplatin (Platinol)Osteosarcoma, skin and nasalcarcinomasCarboplatin (Paraplatin)Skin and nasal carcinomasLobaplatinOsteosarcomaNitrosoureasLomustineBrain and CNS tumors, lymphomas,mast cell tumorsCarmustineBrain tumorsTopoisomerase I inhibitorsCamptothecinsLymphomaHormonesPrednisoneLymphomas and mast celltumorsBiologic Response ModifiersPeroxicam (Feldene)Squamous cell carcinoma, mammaryadenocarcinoma, transmissiblevenereal tumorsMuramyl dipeptideSplenic hemangiosarcoma,osteosarcomaRetinoidsEtretinate (Tegison)Cutaneous lymphoma, mycosisIsotretinoin (Accutane)fungoidesOtherPaclitaxel (Taxol)Mammary carcinomas, lymphomasDarcarbazineRecurrent lymphoma, melanoma,sarcomasL-asparaginase (Elspar)Lymphoid malignancies, mastcell tumors
There are a number of problems and limitations concerning these chemotherapies. For example, as observed in human therapy, these compounds are associated with toxicities linked with the non specific action against dividing cells including bone marrow, gastrointestinal epithelia and hair follicles. Side effects include immunosuppression, anaemia, nausea and vomiting, delayed wound healing, reproductive failure and hair loss. Some specific organs may also be susceptible including heart, kidneys and CNS.
Also, the use of a single chemotherapeutic agent is rarely effective for curing cancer, as not all tumor cells will be effectively killed by a single agent. One reason for this is that as cancer cells develop, so too does the incidence of mutation that may result in resistance phenotypes. Therefore, in most situations it is necessary to develop a combination chemotherapy for the given clinical case.
There is a need for an alternative or improved treatment of cancers of companion animals, and especially those cancers having a higher incidence in companion animals.
There is also a need for an alternative or improved treatment of cancers in dogs.
There is a need for treatment of lymphoma, mast cell tumor, soft tissue sarcoma, hemangiosarcoma, osteosarcoma, squamous cell carcinoma, mammary carcinoma, melanoma, histiocytoma and fibrosarcoma in dogs.
There is also a need for an alternative or improved treatment of cancers in cats.
There is a need for treatment of lymphoma, mast cell tumor, squamous cell carcinoma, mammary carcinoma, hemangiosarcoma, osteosarcoma, fibrosarcoma, and sebaceous hyperplasia/adenoma in cats.